Olefin metathesis is a catalytic process including, as a key step, a reaction between a first olefin and a first transition metal alkylidene complex, thus producing an unstable intermediate metallocyclobutane ring which then undergoes transformation into a second olefin and a second transition metal alkylidene complex according to equation (1) hereunder. Reactions of this kind are reversible and in competition with one another, so the overall result heavily depends on their respective rates and, when formation of volatile or insoluble products occurs, displacement of equilibrium.

Metathesis reactions are extensively applied in the field of chemical reactions, e.g. Ring closing metathesis (RCM), Cross metathesis (CM), Ring opening metathesis (ROM), Ring opening metathesis polymerization (ROMP), acyclic diene metathesis (ADMET), self-metathesis, conversion of olefins with alkynes (enyne metathesis), polymerization of alkynes, and so on.

Typical applications of olefin metathesis but not limited are Reaction Injection Molding (RIM), filament winding, pultrusion of dicyclopentadiene (DCPD), which is an example of the ring opening metathesis polymerization. Industrial application in DCPD polymerization requires latent catalysts, which can allow for longer handling of a monomer-catalyst mixture before the polymerization starts. Other examples of ring opening metathesis polymerization are ROMP of norbornene and its derivatives, copolymerization of different cyclic olefins. Ethenolysis, a chemical process in which internal olefins are degraded using ethylene as the reagent, is an example of cross metathesis; CM of ethene with 2-butene; depolymerization of unsaturated polymers and so fort.
Although homo-coupling (equation 3a) is of high interest, the same is true for cross-coupling between two different terminal olefins (equation 3b). Coupling reactions involving dienes lead to linear and cyclic dimers, oligomers, and, ultimately, linear or cyclic polymers (equation 6). In general, the latter reaction is favoured in highly concentrated solutions or in bulk, while cyclisation is favoured at low concentrations. When intra-molecular coupling of a diene occurs so as to produce a cyclic alkene, the process is called ring-closing metathesis (equation 2). Cyclic olefins can be opened and oligomerised or polymerised (ring opening metathesis polymerisation shown in equation 5). When the alkylidene catalyst reacts more rapidly with the cyclic olefin (e.g. a norbornene or a cyclobutene) than with a carbon-carbon double bond in the growing polymer chain, then a “living ring opening metathesis polymerisation” may result, i.e. there is little termination during or after the polymerization reaction. Strained rings may be opened using an alkylidene catalyst with a second alkene following the mechanisms of the Cross Metathesis. The driving force is the relief of ring strain. As the products contain terminal vinyl groups, further reactions of the Cross Metathesis variety may occur. Therefore, the reaction conditions (time, concentrations, . . . ) must be optimized to favour the desired product (equation 4). The enyne metathesis is a metalcarbene-catalysed bond reorganization reaction between alkynes and alkenes to produce 1,3-dienes. The intermolecular process is called Cross-Enyne Metathesis (7), whereas intramolecular reactions are referred as Ring-Closing Enyne Metathesis (RCEYM).
The cross-metathesis of two reactant olefins, where each reactant olefin comprises at least one unsaturation site, to produce new olefins, which are different from the reactant olefins, is of significant commercial importance. One or more catalytic metals, usually one or more transition metals, usually catalyse the cross-metathesis reaction.
One such commercially significant application is the cross-metathesis of ethylene and internal olefins to produce alpha-olefins, which is generally referred to as ethenolysis. More specific, the cross-metathesis of ethylene and an internal olefin to produce linear α-olefins is of particular commercial importance. Linear α-olefins are useful as monomers or co-monomers in certain (co)polymers poly α-olefins and/or as intermediates in the production of epoxides, amines, oxo alcohols, synthetic lubricants, synthetic fatty acids and alkylated aromatics. Olefins Conversion Technology™, based upon the Phillips Triolefin Process, is an example of an ethenolysis reaction converting ethylene and 2-butene into propylene. These processes apply heterogeneous catalysts based on tungsten and rheniumoxides, which have not proven effective for internal olefins containing functional groups such as cis-methyl oleate, a fatty acid methyl ester.
1-Decene is a co-product typically produced in the cross-metathesis of ethylene and methyl oleate. Alkyl oleates are fatty acid esters that can be major components in biodiesel produced by the transesterification of alcohol and vegetable oils. Vegetable oils containing at least one site of unsaturation include canola, soybean, palm, peanut, mustard, sunflower, tung, tall, perilla, grapeseed, rapeseed, linseed, safflower, pumpkin, corn and many other oils extracted from plant seeds. Alkyl erucates similarly are fatty acid esters that can be major components in biodiesel. Useful biodiesel compositions are those, which typically have high concentrations of oleate and erucate esters. These fatty acid esters preferably have one site of unsaturation such that cross-metathesis with ethylene yields 1-decene as a co-product.
Vegetables oils used in food preparation (fritting of meat, vegetables, . . . ) can be recuperated and after purification, be converted applying e.g. ethenolysis into useful products applicable in biodiesel.
Biodiesel is a fuel prepared from renewable sources, such as plant oils or animal fats. To produce biodiesel, triacylglycerides, the major compound in plant oils and animal fats, are converted to fatty acid alkyl esters (i.e., biodiesel) and glycerol via reaction with an alcohol in the presence of a base, acid, or enzyme catalyst. Biodiesel fuel can be used in diesel engines, either alone or in a blend with petroleum-based diesel, or can be further modified to produce other chemical products.
Several metal-carbene complexes are known for olefin metathesis however the difference between those structures can be found in the carbene part. Patents WO-A-96/04289 and WO-A-97/06185 are examples of metathesis catalysts having the general structure

Where:
M is Os or Ru, R and R1 organic parts from the carbene fragment which have a great structural variability, X and X1 are anionic ligands and L and L1 represents neutral electron donors. “Anionic ligands” are, according the literature in the field of olefin metathesis catalysts, ligands which are negative charged and thus bearing a full electron shell when they are removed from the metal center
A well-known example of this class of compounds is the Grubbs 1st generation catalysts

Another well-known example of this class of compounds is the Grubbs' 2nd generation catalyst which is described in WO-A-0071554 and the hexa-coordinated “Grubbs 3rd generation catalyst described in WO-A03/011455.

There are still some other well-known catalysts described in literature which are very useful in the area of olefin metathesis, and which serve as background information for this application.
Furthermore, other catalysts are known where both carbon atoms of the carbene fragment are bridged; a few of these representatives are given:

The bridged carbene fragment was firstly synthesized by Hill et al. (K. J. Harlow, A. F. Hill, J. D. E. T. Wilton-Ety, J. Chem. Soc. Dalton Trans. 1999, 285-291), however the structure was wrongly interpreted. Fürstner et al. corrected this misinterpretation (J. Org. Chem. 1999, 64, 8275-8280) and a full characterization was described. It followed that reorganization takes place whereby the carbon atoms of the carbene fragment are bridged and generating in this specific case a “3-phenyl-indenylidene carbene” (Chem. Eur. J. 2001, 7, No 22, 4811-4820). Analogues of this catalyst bearing one NHC-ligand and one phosphine ligand where described by Nolan in WO-A-00/15339. These types of compounds are not only catalysts for the olefin metathesis; they also can be used as starting product to produce other ruthenium-carbene compounds via cross metathesis (WO-A-2004/112951).
Furthermore, in US-A-2003/0100776 on page 8, paragraph [0087] are catalysts described where the carbon atoms of the carbene part are bridged and whereby the newly formed cyclic group can be aliphatic or aromatic and can bear substituents or hetero atoms. Additionally, it is said that the generated ring structure is constructed of 4 to 12 and preferable 5 to 8 atoms contains. However, no explicit ring structures or examples are described or given.
For some processes it is desirable that catalyst initiation be controllable. Much less work has focused on decreasing the initiation rate of ruthenium-based catalysts. In these cases, the use of a trigger such as light activation (e.g. photoirradiation), chemical activation (e.g. acid addition), temperature activation (e.g. heating of the sample) or mechanical activation (e.g. ultrason) can help to control initiation. Efficient ring-opening metathesis polymerization (ROMP) reactions require adequate mixing of monomer and catalyst before polymerization occurs. For these applications, catalysts that initiate polymerization at a high rate only upon activation are desirable. However, both Grubbs 2nd gen and Hoveyda 2nd gen. are competent metathesis catalysts at or below room temperature, so alone are not suited for applications where catalyst latency is beneficial (Org. Lett. 1999, 1, 953-956; J. Am. Chem. Soc. 2000, 122, 8168-8179; Tetrahedron Lett. 2000, 41, 9973-9976).
Experimental studies have shown that, for the majority of ruthenium catalysts, dissociation of a donor ligand provides entry to the catalytic cycle. Several design strategies for slowing ligand dissociation can be envisioned. An important consideration is that the method used to slow initiation should not disrupt the catalyst activity. The addition of excess phosphine to the reaction can serve to slow initiation as shown in case I (Scheme 1)(J. Am. Chem. Soc. 1997, 119, 3887-3897). Unfortunately the addition of phosphine commonly results in propagation rates also being reduced.

Another strategy to slow catalyst initiation is to replace the Schrock-type ruthenium carbene with a Fischer carbene (Type II, Scheme 1). This approach has been used to generate several latent metathesis catalysts with Fischer carbenes featuring oxygen, sulphur, and nitrogen substitution. (Organometallics 2002, 21, 2153-2164; J. Organomet. Chem. 2000, 606, 65-74). In some cases, the decrease in activity with these systems is so great that they are considered metathesis-inactive. In fact, addition of ethyl vinyl ether to form a Fischer carbene complex is a standard method of quenching ROMP reactions.
Van der Schaaf and co-workers followed another approach (type IV, scheme 1) to develop the temperature activated, slow initiating olefin metathesis catalyst (PR3)(CI)2Ru(CH(CH2)2—C,N-2-C5H4N) (1 in Scheme 2) in which initiation temperatures were tuned by changing the substitution pattern of the pyridine ring (J. Organomet. Chem. 2000, 606, 65-74). Unfortunately, activities of the reported complexes were undesirably low; restricted to 12000 equiv DCPD. Later, Ung reported on analogous tunable catalytic systems obtained by partially isomerizing trans-(SIMes)(CI)2Ru(CH(CH2)2—C,N-2-C5H4N) (2 in scheme 2) into the cis analogue (Organometallics 2004, 23, 5399-5401). However, none of these catalysts allowed for storage in DCPD monomer for long time as the ROMP of DCPD is completed in 25 minutes after catalyst introduction.

In another methodology towards rationally designed thermally stable olefin metathesis catalyst for DCPD polymerization, efforts were directed towards the development of an O,N-bidentate Schiff base ligated Ru-carbene catalysts elaborated by Grubbs (U.S. Pat. No. 5,977,393; Scheme 3, 4 wherein L=PR3) and Verpoort (WO 03/062253; Scheme 3, 4 wherein L=SIMes and 5 wherein L=PR3, SIMes). It was shown that such complexes are extremely inactive at room temperature towards the polymerization of low-strain, cyclic olefins, allow for storage in DCPD for months and can be thermally activated to yield increased activity for the bulk-polymerization of DCPD, but from industrial point of view, catalysts of which their performance is easy tunable by a simple straightforward modification are not described (EP1468004; J. Mol. Cat. A: Chem. 2006, 260, 221-226).

Recently a series of latent olefin metathesis catalysts bearing bidentate K2—(O,O) ligands were synthesized (Scheme 3, 3). Complex 3, proved to be inactive for the solvent-free polymerization of DCPD. It was furthermore illustrated that complex 3 (Scheme 3, L=PCy3, SIMes) is readily activated upon irradiation of a catalyst/monomer mixture containing a photoacid generator and was found applicable in ROMP of DCPD (WO 99/22865). Nevertheless irradiation of a solution of DCPD and 3 (L=SlMes) in a minimal amount of CH2CI2 resulted in complete gelation within 1 h but solidified and cross-linked monomer was not obtained.
This indicates low catalyst activity and the operation on a low amount of the active species. Summarizing, the latent catalysts are of prominent importance for Ring-Opening Metathesis Polymerizations of low-strained cyclic olefins, as they allow for mixing of monomer and catalyst without concomitant gelation or microencapsulation of the precatalyst.
All the above-described catalysts bearing an indenylidene carbene part are based on a non-chelating phenyl-indenylidene structure without any substituents or functional groups. Catalysts with a chelating phenyl-indenylidene structure have been described in PCT/US2010/059703 (WO 2011/100022 A2) an indenylidene based catalyst is described whereby one phosphine ligand is substituted by a neutral donor ligand which is linked to the indenylidene carbene. The resulting catalyst is a 3-phenylindenylidene Hoveyda analogue catalyst.
In PCT/US2011/029690 (WO 2011/119778 A2) a hexa-coordinated catalyst is claimed, however in this document no catalysts were isolated; a synthetic method for the in-situ generation of olefin metathesis catalysts is disclosed since according to Schrödi the synthesis of these complexes is relatively cumbersome. The synthesis usually involves more than one step and requires isolation of the catalysts to remove catalyst-inhibiting byproducts such as liberated phosphines. The resulting in-situ generated catalysts are all phenylindenylidene Hoveyda analogue catalysts.
Other non-chelating indenylidene catalysts bearing functional groups or substituents on the indenylidene part, different from phenylindenylidene, are until now not known.

In WO 2011/009721 A1 bis-Schiff base catalysts are described on page 18-20 “via route B” starting from 5 with L=SIMes wherein it is said that the reaction mixture was investigated with 1H and 31P NMR revealing a quantitative transformation to the desired bis-Schiff Base catalyst. However, none of those compounds contain any P-ligand. Furthermore, the catalysts prepared via “route A” were investigated with 1H and 31P NMR revealing a quantitative transformation to the desired bis-Schiff Base catalyst, though, no values are given.
Moreover, it is said that the bis-Schiff base catalyst (catalyst 4 on page 22) has an extreme latent character even at 200° C. (catalyst 4/DCPD ratio: 1/15000) as was proven with DSC. However, it is well-know that DCPD when heated above 150° C., undergoes a retro-Diels-Alder reaction to yield cyclopentadiene and the boiling point is 170° C.
Additionally, it is said in the “summary of the invention” page 4 that the catalysts are obtained by a simple, efficient, green and highly yielding synthetic process. However, the catalysts procedure for the catalysts synthesis is 72 h (without purification steps) which can not be called “efficient” or industrial attractive. Besides of all the synthesized catalysts no yield is mentioned.
The ruthenium carbene part (indenylidene) in WO 2011/009721 A1 is defined as in WO 00/15339. The most preferably carbene part is a phenylindenylidene ligand. Yet, no substituted phenylindenylidene ligands are claimed.
Despite the advances achieved in the preparation and development of olefin metathesis catalysts, a continuing need exists for new improved synthetic methods and new catalysts. Of particular interest are methods that provide the preparation of new catalysts, which easily can be prepared on industrial scale.
Notwithstanding the different available catalysts, from industrial point of view, catalysts of which their performance is easy tunable by a simple straightforward modification are highly desired. Of particular interest are catalysts which can be modified from completely latent to highly active; latent catalysts find easily application in ROMP e.g. DCPD polymerization via RIM, highly active catalysts find easily application in cross metathesis e.g. ethenolysis.
Moreover, easy tunable catalysts can be obtained by tuning of the electron density of the catalyst by variation of the alkylidene (e.g. indenylidene) in combination with ligands (e.g. ditopic or multitopic ligands). However, the combination of non-chelating substituted/functionalised indenylidene with ditopic or multitopic ligands is still not existing and offers extra advantage in terms of initiation tunability which results in catalysts which can be varied from real latent to highly active.
Additionally, the catalysts of present invention afford latent catalysts stable in the monomer and highly active after an industrially acceptable activation process, a property of which there is still a high demand.
Furthermore, the instant invention's metathesis catalyst compounds provide both a mild and commercially economical and an “atom-economical” route to desirable olefins, which in turn may be useful in the preparation of linear alpha-olefins, unsaturated polymers, cyclic olefins, etc. . . . .
Another important parameter for the evaluation of metathesis catalysts is the need for catalysts that can be separated from the final metathesis product easily. For applications of metathesis reactions in pharmaceutical industry, the ruthenium level in drugs must not exceed 5 ppm. (http://www.emea.europa.eu/pdfs/human/swp/444600en.pdf for EMEA regulations) Up to date, different protocols were reported to remove ruthenium from metathesis products to meet these criteria. The employed protocols include removal of ruthenium by oxidation reactions (H2O2, PPh3O, DMSO or Pb(OAc)4, water extraction, scavengers, supported phosphine ligands, or treatment with active charcoal combined with chromatography. These protocols only decreased the ruthenium concentration in the final product to 100-1200 ppm, which is far from the required criteria for pharmaceutical applications. The immobilization of catalysts (organic or inorganic support) gave promising results with moderate success for efficient removal of ruthenium. As another strategy, modification of the ligands by more polar groups or alternation of their steric hindrance to ease their separation from metathesis products was also reported. Grela successfully modified Hoveyda-Grubbs type catalysts with ionic-tagged ligands which exhibits a good affinity towards silica gel. (Green Chem., 2012, 14, 3264.) However, the synthesis of an ionic-tagged ligand is cumbersome. The catalysts of this invention, obtained via a straightforward synthesis procedure, show an extremely high affinity for silica especially catalysts bearing multitopic ligands making them extremely useful and attractive for pharmaceutical and fine chemical applications.
The synthesis of RuCl2(PCy3)2(3-phenylindenylidene) has proven useful in providing an easy route to ruthenium alkylidenes which avoids costly diazo preparations (Platinum Metals Rev. 2005, 49, 33).
In order to obtain an economically viable process for linear α-olefins (e.g. 1-decene) production via the cross-metathesis of ethylene and biodiesel (such as animal or vegetable oils), higher activity catalysts or more stable catalysts must be developed. Moreover, there is still a need for the development of catalysts with equivalent or better performance characteristics but synthesized directly from less expensive and readily available starting materials.
As there is a continuous need in the art for improving catalyst efficiency, i.e. improving the yield of the reaction catalysed by the said catalyst component after a certain period of time under given conditions (e.g. temperature, pressure, solvent and reactant/catalyst ratio) or else, at a given reaction yield, providing milder conditions (lower temperature, pressure closer to atmospheric pressure, easier separation and purification of product from the reaction mixture) or requiring a smaller amount of catalyst (i.e. a higher reactant/catalyst ratio) and thus resulting in more economic and environment-friendly operating conditions. This need is still more stringent for use in reaction-injection molding (RIM) processes such as, but not limited to, the bulk polymerisation of endo- or exo-dicyclopentadiene, or formulations thereof.
There is also a specific need in the art, which is yet another goal of this invention, for improving reaction-injection molding (RIM) processes, resin transfer molding (RTM) processes and reactive rotational molding (RRM) processes such as, but not limited to, the bulk polymerisation of endo- or exo-dicyclopentadiene, or copolymerization thereof with other monomers, or formulations thereof. More specifically there is a need to improve such processes which are performed in the presence of multicoordinated transition metal complexes, in particular ruthenium complexes. All the above needs constitute the various goals to be achieved by the present invention; nevertheless other advantages of this invention will readily appear from the following description.